Acid sensor ASIC1a induces synovial fibroblast proliferation via Wnt/β-catenin/c-Myc pathway in rheumatoid arthritis

被引:4
|
作者
Xu, Yayun [1 ,3 ,4 ]
Lu, Zheng [2 ,3 ,4 ]
Ling, Yian [2 ,3 ,4 ]
Hou, Ruirui [2 ,3 ,4 ]
Tao, Jingjing [2 ,3 ,4 ]
Deng, Ge [2 ,3 ,4 ]
Xu, Xiaoling [2 ,3 ,4 ]
Chen, Xuewei [2 ]
Ruan, Jingjing [5 ]
Zhang, Yihao [6 ,7 ]
Peng, Xiaoqing [5 ]
Chen, Feihu [1 ,2 ,3 ,4 ]
机构
[1] Anhui Med Univ, Sch Publ Hlth, Hefei, Peoples R China
[2] Anhui Med Univ, Sch Pharm, Hefei, Peoples R China
[3] Anhui Inst Innovat Drugs, Inflammat & Immune Mediated Dis Lab Anhui Prov, Hefei, Peoples R China
[4] Anhui Med Univ, Anhui Prov Key Lab Major Autoimmune Dis, Hefei, Peoples R China
[5] Anhui Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Hefei, Peoples R China
[6] Anhui Med Univ, Sch Publ Hlth, Dept Toxicol, Hefei, Peoples R China
[7] Anhui Higher Educ Inst, Key Lab Environm Toxicol, Hefei, Peoples R China
基金
中国国家自然科学基金;
关键词
Rheumatoid arthritis; ASIC1a; Synovial fibroblasts; Wnt; -catenin pathway; Proliferation; BETA-CATENIN; PH; MECHANISMS; PROMOTES; GROWTH; CELLS;
D O I
10.1016/j.intimp.2022.109328
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and progressive joint destruction in the middle and late stages. Notably, activated rheumatoid arthritis synovial fibroblasts (RASFs) exhibit tumor-like features, including an increased proliferation rate that largely contributes to pannus formation and joint destruction. Our previous studies have demonstrated that acid-sensing ion channel 1a (ASIC1a) was highly expressed in RASFs, and acidic microenvironment of synovial fluid in patients with RA can activate ASIC1a to promote synovial inflammation, leading to the progression of RA. However, the role and possible mechanism of ASIC1a in RASF proliferation remains unclear. The present study aimed to investigate the effect of ASIC1a activation upon acidosis on RASF proliferation and its molecular mechanism in vivo and in vitro. The results of in vitro experiments showed that activation of ASIC1a upon acidosis promoted the proliferation of RASFs, which could be attenuated by the specific ASIC1a inhibitor Psalmotoxin-1 (PcTx-1) or specific siRNA for ASIC1a. Mechanistically, Wnt/beta-catenin/c-Myc signaling pathway was involved in ASIC1a-induced RASF proliferation. The results of in vivo experiments indicated that intra-articular injection of PcTx-1 reduced synovial hyperplasia and ameliorated cartilage degradation in rats with adjuvant arthritis (AA). Collectively, these results suggest that activation of ASIC1a upon acidosis promotes RASF proliferation, and the mechanism may be related to Wnt/beta-catenin/c-Myc pathway.
引用
收藏
页数:12
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